Shorter telomeres, accelerated ageing and increased lymphoma in DNA-PKcs-deficient mice
| Autor: | Peter Klatt, Silvia Espejel, Marta Martín, Juana M. Flores, Juan Martín-Caballero, Maria A. Blasco |
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| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Male
Aging DNA Repair Lymphoma DNA repair DNA damage Scientific Report Context (language use) DNA-Activated Protein Kinase Biology Protein Serine-Threonine Kinases Biochemistry Chromosomes Mice Life Expectancy Testis Genetics Animals Nuclear protein Molecular Biology DNA-PKcs Mice Knockout Body Weight Cell Cycle Nuclear Proteins Cell cycle Telomere Molecular biology Spine Cell biology DNA-Binding Proteins Mice Inbred C57BL enzymes and coenzymes (carbohydrates) Meiosis Ageing Female biological phenomena cell phenomena and immunity DNA Damage |
| Popis: | Non-homologous end joining (NHEJ) is the principal repair mechanism used by mammalian cells to cope with double-strand breaks (DSBs) that continually occur in the genome. One of the key components of the mammalian NHEJ machinery is the DNA-PK complex, formed by the Ku86/70 heterodimer and the DNA-PK catalytic subunit (DNA-PKcs). Here, we report on the detailed life-long follow-up of DNA-PKcs-defective mice. Apart from defining a role of DNA-PKcs in telomere length maintenance in the context of the ageing organism, we observed that DNA-PKcs-defective mice had a shorter life span and showed an earlier onset of ageing-related pathologies than the corresponding wild-type littermates. In addition, DNA-PKcs ablation was associated with a markedly higher incidence of T lymphomas and infections. In conclusion, these data link the dual role of DNA-PKcs in DNA repair and telomere length maintenance to organismal ageing and cancer. |
| Databáze: | OpenAIRE |
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